This is an omnibus project that covers a number of studies on developmenting these methods to determine the basic chemical and physiological mechanisms that mediate the functional activation of brain blood flow and metabolism that are now used so extensively to study cognitive and other functions. Much of the work in this project during the last year has been directed at elucidating the chemical mechanisms of regulation of cerebral blood flow. These results have shown that adenosine receptors and K+ channels in vascular smooth muscle are involved and that adenosine production by alterations in brain tissue metabolism initiates a cascade of events that act on the adenosine receptors and ends in the opening of the K+ channels, membrane hyperpolarization, and smooth muscle relaxation in the cerebral blood vessel walls. Publications Dienel, G.A., Cruz, N.F., Adachi, K., Sokoloff, L., and Holden, J.E. (1997) Determination of local brain glucose level with [14C]methylglucose: Effects of glucose supply and demand. Am. J. Physiol. (Endocrinol. Metab. 36), 273: E839-E849. Takahashi, S., and Sokoloff, L. (1997) Role of nitric oxide in the regulation of cerebral blood flow in conscious rats. In: Ishimura, Y. (Ed.): Oxygen Homeostasis and its Dynamics, Springer-Verlag, Tokyo, pp. 545-563. Horinaka, N., Kuang, T-Y, Pak, H., Wang, R., Jehle, J., Kennedy, C., and Sokoloff, L. (1997) Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats. J. Cereb. Blood Flow Metab 17: 1309-1318. In Press: Sokoloff, L., (In press) Mapping cerebral functional activity with radioactive deoxyglucose. In: Adelman, G., and Smith B., (Eds.): Encyclopedia of Neuroscience, Second Edition, Amsterdam, Elsevier. Clark, D.D. and Sokoloff, L. (In press) Circulation and energy metabolism of the brain. In: Siegel, G., Agranoff, B., Albers, R.W., and Fisher, S. (Eds.): Balsic Neurochemistry: Molecular, Cellular, and Medical Aspects, Sixth Edition, Lippincott-Raven, Philadelphia. Turkheimer, F., Sokoloff, L., Bertoldo, A., Lucignani, G., Reivich, M., Jaggi, L.J., and Schmidt, K. (In press) Estimation of uncertainty in components determined with spectral analysis. J. Cereb. Blood Flow Metab (accepted March 11, 1998). Sokoloff, L. (In press) Mechanisms of regulation of cerebral blood flow. In: Ito, U., Kirino, T., Kuroiwa, T., and Klatzo, I. (Eds.): Maturation Phenomenon in Cerebral Ischemia III. Defensive Mechanisms versus Apoptosis; Neuronal Recovery and Protection in Infarction, Springer, Berlin. Sokoloff, L. (In press) Energetics of functional activation in neural tissues. Neurochem. Res. (Accepted July 27, 1998). Sokoloff, L., Kuang, T-Y, Horinaka, N., and Kennedy, C. (In press) Are cerebral circulation and energy metabolism really tightly coupled? In: Krieglstein, J. (Ed.): Pharmacology of Cerebral Ischemia 1998. medpharm Scientific Publishers, Stuttgard, 1998. Madsen, P.L., Cruz, N.F., Sokoloff, L., and Dienel, G.A. (In press) Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: Excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue. J. Cereb. Blood Flow Metab. (Accepted August 14, 1998).